A male patient in his late 40s presented with swelling over the nape of
the neck for 3 years, which was gradually progressive. He was a known case of
HIV disease on AntiRetroviral Therapy (ART) for 15 years. Since last 3 years
patient is on zidovuine (ZDV), lamivudine (3TC) and dolutegravir (DTG) regimen
from Governmental ART centre. Initial size of the swelling was around 5×5 cm
and progressed to present size of around 20×15 cm over 3 years. It was
associated with dull aching pain. The patient could not lie supine due to the
enormous swelling and had to sleep in a lateral position. On examination the
swelling was in nape of neck, diffuse in subcutaneous plane and around 20×15 cm
size. Patient also had features of lipodystrophy in face and abdomen. Routine
blood investigations were normal, CD4 counts were 386 cells/mm3. RNA
viral load was <50 copies/ml. He underwent MRI of neck, it showed non
capsulated cervico-dorsal subcutaneous fat proliferation, underlying muscles
appeared normal with no significant cervical lymphadenopathy. The decision to
operate was taken as the patient was symptomatic, and lipohypertrophy was
causing a significant disturbance in his sleep (fig. 1, 2).
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The patient underwent excision of the swelling under general anaesthesia
(fig. 3). Excised specimen weighed 750 grams (fig. 4). Post-operative period
was uneventful. Histopathology report showed features suggestive of lipoma.
Modification in ART regime was done, zidovudine was switched to tenofovir. On
follow-up wound was healthy, patient’s symptoms significantly improved.
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Case 2
A 16-year-old girl presented with diffuse swelling over her nape of
neck, involving the upper back for 10 years. She had difficulty while lying in
supine position because of the size of swelling, however, there were no
restrictions in neck movements. No abnormal deposition of fat anywhere else in
the body. She was detected since birth with the retroviral disease and is
compliant on her anti-retroviral regimen (zidovudine 300 mg twice daily;
lamivudine 150 mg twice daily; dolutegravir 50 mg once daily). She has a
positive family history of retroviral disease related to her parents.
Physical examination revealed a diffuse swelling over nape of neck
approximately 30×20 cm, non-tender, soft in consistency extending till lower
border of scapula (fig. 5). Absolute CD4 count, HIV-1 RNA viral load and
antibodies to HIV (done by chemiluminescence method) were 993.49 cells/μl,
<40 copies/ml and reactive, respectively.
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Ultrasound of the neck revealed a large ill-defined iso-hyperechoic
30×20 cm lesion with sub-cutaneous fat like echogenicity, at posterior aspect
of neck, upper back and interscapular region. Features were suggestive of
cervico-dorsal fat pad/lipomatosis.
The patient underwent surgical excision of this swelling due to cosmetic
concerns and inability to sleep (fig. 6, 7). Excised specimen weighed 800 grams
(fig. 8). Postoperative period was uneventful. Based on review done by
Infectious Disease Department before discharge, Zidovudine was switched to
tenofovir. On follow-up, wound was healthy, patient’s symptoms improved.
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Discussion
ART induced lipodystrophy can present either with lipohypertrophy (fat
accumulation) or lipoatrophy (fat loss) or these two distinct manifestations
may coexist as well. Lipohypertrophy usually exhibited symptoms of buffalo hump
(dorsocervical fat pad) or fat accumulation in abdominal wall, breasts, thighs,
gluteal region and anterior neck. On the other hand, lipoatrophy is
characterized by fast loss in subcutaneous tissue in arms, legs, face and
buttocks [4].
The causes of lipodystrophy are multifactorial, and includes patient and
treatment factors. Older age (older than 40 years of age) [4-7], female sex [8,
9], elevated serum triglyceride level [10], low nadir CD4 cell count [11] and
an advanced stage of HIV infection [12] have all been identified as risk
factors for lipodystrophy.
Nucleoside reverse transcriptase inhibitors (NRTI(s) are most often
associated with lipoatrophy and protease inhibitor (PI(s) based regimen are
associated with lipohypertrophy. NRTIs are strongly associated with the loss of
subctaneous fat and hyperlactatemia due to mitochondrial damage, while PIs are
more closely associated with lipoaccumulation and effects on lipid metabolism
and insulin resistance due to dysfunction in adipocyte differentiation. The effects
of NRTIs appear to be augmented or accelerated when combined with PI [13, 14],
and the manifestations of lipodystrophy are different than in patients
receiving NRTIs alone [11, 13].
Treatment options for patients with lipohypertrophy, holistically are as
follow: since risk factors for lipohypertrophy are more of host factors like
high caloric diet, female gender, higher body fat % at baseline and therefore,
dietary counselling and lifestyle modifications (combination of strength and
cardiovascular training) helps to prevent the risk of fat accumulation again
[1, 4].
Patients on protease inhibitors, can be prescribed with lose-dose
atorvastatin (pravastatin) orfluvastatin with dose adjustments to avoid statin
toxicity [1].Consultation of psychology department should be sought, in view of
associated poor body image and anxiety [4].
Lipohypertrophy is surgically treated by liposuction or lipectomy. In a
retrospective study done in 2021 [15], on 9 HIV-positive patients with
lipodystrophy, 5 of them had undergone liposuction, out of which 3 (60%) had
experienced recurrence and 1 had seroma formation. However, rest 4 patients who
underwent lipectomy had 0 recurrences and 1 seroma complication in follow up.
Warren et al. [16] study showed 7 patients undergoing
excision lipectomy with no recurrence on 26 month follow up.
Hultman et al. [17] showed that despite the potential for recurrence,
surgical management of HIV-associated lipodystrophy was efficacious with
minimal morbidity. Ultrasonic assisted liposuction and suction assisted
lipectomy were particularly beneficial in reducing the cervicodorsal fat pad.
Barton et al. [15] compared excision lipectomy and
liposuction and concluded excisional lipectomy as the primary treatment that
considering the limitations of liposuction alone as the primary intervention.
Both patient in our study underwent excision lipectomy due to diffuse
and enormous size of the swelling.
Lipohypertrophy can cause decreased self-esteem, quality of life, and
social stigma due to visible abnormality. It can also have a significant effect
on drug adherence.
There is no consensus on the most effective therapy for lipodystrophy.
Switching of drug regimens alone may not alter the course of lipodystrophy.
Hence, managing large cervicodorsal lipohypertrophy is mainly surgical, along
with the change of ART regimen.
Conclusion
• HIV-associated lipodystrophy progressively worsens when protease
inhibitors and thymidine analog NRTIs therapy continues.
• Altering body image and self-esteem may lead to poor compliance with
antiretroviral therapy and treatment failure.
• Early identification and management of HIV-associated metabolic
complications can halt the progression of these conditions and, in some cases,
may help reverse lipodystrophy.
• Surgical management remains the mainstay with excision lipectomy and
ultrasonic liposuction as preferred modalities
References
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